Biochimie最新文献

英文中文

Assessing the role of E451, D452, and H139 in the catalytic function of a Thermus thermophilus bacterial laccase 评价E451、D452和H139在嗜热热菌漆酶催化功能中的作用

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2026-01-27 DOI: 10.1016/j.biochi.2026.01.010

R. Miranda-Blancas , M.C. Cardona-Echavarría , G. Saab-Rincón , C. Millán-Pacheco , A. Landa , E. Rudiño-Piñera

Laccases are oxidoreductase enzymes that require four electrons and four protons for each catalytic cycle to trigger the conversion of one oxygen molecule into two water molecules. However, for bacterial laccases, including the laccase from Thermus thermophilus HB27 (Tth-MCO), the complete proton transfer pathway from the solvent-exposed surface of the protein to the trinuclear center remains unclear. This paper describes new crystallographic structures of a partially copper-occupied Tth-MCO, subjected to a cumulative X-ray radiation strategy to uncover the effect of the X-ray driven chemical reduction on the residues related to the enzyme's proton relay. Additionally, we constructed and analyzed single and double mutants of residues H139 and E451 to assess their effect on the kinetic parameters of Tth-MCO. The proper folding of the mutants was evaluated using circular dichroism, while the structural stability of the mutants was analyzed using molecular dynamics calculations based on AlphaFold 2 models. Such analysis of the structural and kinetic data obtained provides deeper insights into the amino acids involved in the proton relay mechanism of Tth-MCO. Considering the conservation of amino acids involved in several bacterial laccase sequences, the proposed multi-step proton relay mechanism may also exist in other bacterial laccases.

漆酶是氧化还原酶，每个催化循环需要四个电子和四个质子来触发一个氧分子转化为两个水分子。然而，对于细菌漆酶，包括来自嗜热热菌HB27 （th- mco）的漆酶，从溶剂暴露的蛋白质表面到三核中心的完整质子转移途径尚不清楚。本文描述了部分铜占据的th- mco的新晶体结构，并进行了累积x射线辐射策略，以揭示x射线驱动的化学还原对酶的质子接力相关残基的影响。此外，我们构建并分析了H139和E451残基的单突变体和双突变体，以评估它们对th- mco动力学参数的影响。利用圆二色性评价突变体的适当折叠，利用基于AlphaFold 2模型的分子动力学计算分析突变体的结构稳定性。通过对结构和动力学数据的分析，可以更深入地了解th- mco质子接力机制中涉及的氨基酸。考虑到一些细菌漆酶序列所涉及的氨基酸的保守性，所提出的多步质子接力机制可能也存在于其他细菌漆酶中。

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引用次数: 0

Leptin increases lipid storage in Sertoli cells: Signaling pathways and cellular mechanisms involved 瘦素增加脂质储存在支持细胞：信号通路和细胞机制参与。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2026-01-22 DOI: 10.1016/j.biochi.2026.01.009

Marina Ercilia Dasso, Cecilia Lucia Centola, Florencia Nerea Tabares, María Noel Galardo, Silvina Beatriz Meroni, María Fernanda Riera

Leptin is an adipokine with a role in male reproductive function. Sertoli cells (SCs) express leptin receptors, but leptin effects on SCs’ functions have been scarcely researched. SCs support germ cell development by providing various compounds, including transferrin and ketone bodies. Additionally, SC oxidize fatty acids (FAs) as their primary energy source and store them as triacylglycerols (TAGs) within lipid droplets (LDs), which serve as a crucial energy reserve within SCs. In the present study, we investigated whether leptin regulates the secretion and lipid storage in SCs and identified the potential signaling pathways involved. SC cultures were obtained from 20-day-old rats. The results show that leptin does not modify transferrin or 3-hydroxybutyrate secretion. However, it increases LD content and TAG levels in SCs. Leptin also augments the mRNA levels of FA transporter FAT/CD36, glycerol-3-phosphate-acyltransferase 3, and perilipin 1. We then explored the activation and the involvement of JAK/STAT3, PI3K/AKT, mTORC1/p70S6K, and PPARɣ-dependent pathways. Leptin treatment increases phosphorylated STAT3, AKT, and p70S6K levels. Also, leptin augments PPARɣ mRNA levels. In addition, we observed that Wortmannin (PI3K inhibitor), Rapamycin (mTORC1 inhibitor), and T0070907 (PPARɣ antagonist) decrease leptin-stimulated LD content, but Stattic (STAT3 inhibitor) has no effect. These results suggest that leptin regulates LD content through the activation of PI3K/AKT, mTORC1/p70S6K, and PPARɣ-dependent pathways. This study reveals that leptin increases lipid storage in SCs, a role that may help meet the seminiferous tubules' demand for FAs.

瘦素是一种与男性生殖功能有关的脂肪因子。支持细胞（SCs）表达瘦素受体，但瘦素对其功能的影响研究甚少。干细胞通过提供包括转铁蛋白和酮体在内的多种化合物来支持生殖细胞的发育。此外，SC氧化脂肪酸（FAs）作为其主要能量来源，并将其作为三酰基甘油（TAGs）储存在脂滴（ld）中，脂滴在SC中充当重要的能量储备。在本研究中，我们研究了瘦素是否调节SCs的分泌和脂质储存，并确定了可能参与的信号通路。从20日龄大鼠获得SC培养物。结果表明，瘦素不影响转铁蛋白和3-羟基丁酸盐的分泌。然而，它增加了sc中的LD含量和TAG水平。瘦素还能增加FA转运体FAT/CD36、甘油-3-磷酸酰基转移酶3和佩里平1的mRNA水平。然后，我们探索了JAK/STAT3、PI3K/AKT、mTORC1/p70S6K和PPAR依赖性通路的激活和参与。瘦素治疗增加磷酸化STAT3、AKT和p70S6K水平。此外，瘦素增加PPAR α mRNA水平。此外，我们观察到Wortmannin （PI3K抑制剂），Rapamycin （mTORC1抑制剂）和T0070907 （PPAR α拮抗剂）降低瘦素刺激的LD含量，但Stattic （STAT3抑制剂）没有影响。这些结果表明，瘦素通过激活PI3K/AKT、mTORC1/p70S6K和PPAR依赖性通路来调节LD含量。这项研究表明，瘦素增加了SCs中的脂质储存，这一作用可能有助于满足精管对FAs的需求。

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引用次数: 0

Inside front cover-EDB 内部前盖- edb

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2026-01-20 DOI: 10.1016/S0300-9084(26)00007-6

引用次数: 0

SUMOylation and anticancer drug resistance SUMOylation与抗癌耐药。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2026-01-18 DOI: 10.1016/j.biochi.2026.01.007

Hongwei Zhao, Chao Huang

Therapeutic resistance is a major obstacle in cancer treatment, often leading to recurrence and death. SUMOylation is a dynamic and reversible process of post-translational modification through a strict enzyme cascade that regulates the modification of target proteins by SUMO1-5 and SENP family proteins, which are involved in regulating protein stability, function, and localization to influence biological pathways, including cancers. SUMOylation contributes significantly to cancer drug resistance, undermining the efficacy of clinical treatment. Therefore, studying the role of SUMOylation in the development of cancer drug resistance has significant prospects. This review focuses on the important mechanistic role of SUMOylation in promoting or inhibiting cancer drug resistance and summarizes the feasibility of using SUMOylation as a therapeutic target for cancer treatment by combining SUMOylation inhibitors and anticancer drugs, which will provide new insights into overcoming cancer drug resistance and clinical cancer treatment.

治疗耐药性是癌症治疗的主要障碍，经常导致复发和死亡。SUMOylation是一个动态可逆的翻译后修饰过程，通过严格的酶级联调节SUMO1-5和SENP家族蛋白对靶蛋白的修饰，这些蛋白参与调节蛋白质的稳定性、功能和定位，从而影响包括癌症在内的生物途径。SUMOylation对肿瘤耐药有重要作用，影响临床治疗效果。因此，研究SUMOylation在肿瘤耐药发展中的作用具有重要的前景。本文综述了SUMOylation在促进或抑制肿瘤耐药中的重要机制作用，并总结了SUMOylation抑制剂与抗癌药物联合使用作为肿瘤治疗靶点的可行性，这将为克服肿瘤耐药和临床癌症治疗提供新的见解。

引用次数: 0

Recent advances in protein synthesis inhibitors 蛋白质合成抑制剂的最新进展。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2026-01-13 DOI: 10.1016/j.biochi.2026.01.005

Alisa P. Chernyshova , Petr V. Sergiev , Dmitrii A. Lukianov , Vera A. Alferova

Antimicrobial resistance threatens the long-standing efficacy of antibiotics and underscores the need to expand, refine, and diversify antimicrobial therapies. Translation is a uniquely druggable process: its machinery is essential, conserved in bacteria, and sufficiently divergent from the eukaryotic counterpart to enable selectivity. This review synthesizes recent progress on inhibitors of initiation, elongation, termination, and recycling. High-resolution structural and biophysical studies have resolved longstanding ambiguities, reassigned ribosomal binding sites, uncovered stage-specific activities in scaffolds previously thought to act elsewhere, and revealed multistage, context-dependent mechanisms. Beyond the canonical stages, quality-control pathways that offer orthogonal points of intervention were observed. Collectively, these advances support structure-guided, context-aware, and hybrid/combination strategies for antibiotic design and therapeutic development.

抗菌素耐药性威胁到抗生素的长期疗效，并强调需要扩大、改进和多样化抗菌素治疗。翻译是一种独特的可药物化过程：其机制是必不可少的，在细菌中是保守的，并且与真核生物的对应物有足够的差异，从而具有选择性。本文综述了引发、延伸、终止和再循环抑制剂的最新研究进展。高分辨率结构和生物物理研究解决了长期存在的模糊性，重新分配了核糖体结合位点，揭示了以前认为在其他地方起作用的支架的阶段特异性活性，并揭示了多阶段，环境依赖的机制。在规范阶段之外，观察到提供正交干预点的质量控制途径。总的来说，这些进展支持结构导向、环境感知和混合/联合策略，用于抗生素设计和治疗开发。

引用次数: 0

Human CELA1 has pancreatic elastase-like activity 人CELA1具有胰腺弹性酶样活性。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2026-01-09 DOI: 10.1016/j.biochi.2026.01.004

Deepti Jamwal , Prince Kumar , Kunal Meena , Vikash Yadav , Rajesh Kumar , Nidhi Adlakha , Supratik Das

CELA3A and CELA3B are the primary elastases secreted by the human pancreas that are digestive enzymes and are markers for pancreatic exocrine insufficiency. CELA1, another family member, is not expressed in the human pancreas but has been detected in the mouse lung and human keratinocytes. However, the enzymatic activity and mechanism of function of human CELA1 has not been previously demonstrated. Here, we show using purified, recombinant pro-hCELA1, that it is activated by trypsin and has pancreatic elastase-like activity. We show that pro-hCELA1 cleavage by trypsin is blocked by aprotinin. We have determined the enzyme kinetics of the active fraction of recombinant hCELA1 and show that it follows steady-state kinetics with a higher substrate affinity than commercial porcine pancreatic elastase.

CELA3A和CELA3B是人类胰腺分泌的主要弹性酶，是消化酶，是胰腺外分泌不足的标志。CELA1是另一个家族成员，在人类胰腺中不表达，但在小鼠肺和人类角化细胞中检测到。然而，人类CELA1的酶活性和功能机制尚未被证实。在这里，我们使用纯化的、重组的pro-hCELA1，证明它被胰蛋白酶激活，并具有胰腺弹性酶样活性。我们发现胰蛋白酶对前hcela1的切割被抑酶蛋白阻断。我们已经确定了重组hCELA1活性部分的酶动力学，并表明它遵循稳态动力学，具有比商品猪胰腺弹性酶更高的底物亲和力。

引用次数: 0

Human mitochondrial persulfide dioxygenase is potently and reversibly inhibited by nitric oxide 人线粒体过硫双加氧酶被一氧化氮有效和可逆地抑制。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2026-01-05 DOI: 10.1016/j.biochi.2026.01.001

Francesca Giordano , Diogo H.P. Silva , Elena Forte , Alessandro Giuffrè , João B. Vicente

Hydrogen sulfide (H₂S) regulates multiple human physiological processes, its reactivity and range of action being tightly controlled through regulation of H₂S-synthesizing and -detoxifying enzymes. H₂S detoxification is mainly achieved by a mitochondrial sulfide detoxifying pathway including persulfide dioxygenase (PDO). Human PDO (known as ethylmalonic encephalopathy protein 1, ETHE1), a homodimeric enzyme with a mononuclear iron centre active site, catalyzes the conversion of glutathione persulfide (GSSH) and O₂ to reduced glutathione (GSH) and sulfite. Here we report that ETHE1 is potently inhibited by authentic nitric oxide (NO) gas at physiological concentrations, as observed by high resolution respirometry. Inhibition is reversible, occurs via NO binding to the reduced mononuclear iron center and becomes more potent and persistent at lower O₂ levels. Incubation with s-nitrosoglutathione (GSNO) also appears to partially and transiently inhibit ETHE1, this effect likely resulting from s-nitrosation of cysteine residues. While ETHE1 is devoid of NO reductase activity, in aerobic conditions it displays low NO degrading activity. These findings unravel a novel layer of cross-regulation between the H₂S and NO gasotransmitters with possible implications on the regulation of numerous physiological and pathophysiological processes.

硫化氢（H2S）调节着人体多种生理过程，其反应活性和作用范围通过调控硫化氢合成酶和解毒酶而受到严格控制。H2S解毒主要通过包括过硫双加氧酶（PDO）在内的线粒体硫化物解毒途径实现。人类PDO（被称为乙基丙二酸脑病蛋白1，ETHE1）是一种具有单核铁中心活性位点的二聚体酶，催化谷胱甘肽过硫（GSSH）和O2转化为还原性谷胱甘肽（GSH）和亚硫酸盐。在这里，我们报告了ETHE1在生理浓度下被真实的一氧化氮（NO）气体有效抑制，正如高分辨率呼吸测量所观察到的那样。抑制是可逆的，通过NO与还原的单核铁中心结合发生，并且在较低的O2水平下变得更有效和持久。用s-亚硝基谷胱甘肽（GSNO）孵育也可以部分和短暂地抑制ETHE1，这种作用可能是由半胱氨酸残基的s-亚硝化引起的。虽然ETHE1缺乏NO还原酶活性，但在有氧条件下，它表现出较低的NO降解活性。这些发现揭示了H2S和NO气体递质之间交叉调节的新层面，可能对许多生理和病理生理过程的调节产生影响。

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引用次数: 0

Phase separation in regulation of gene expression: current methodological and conceptual approaches 基因表达调控的相分离：当前的方法和概念方法。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2026-01-05 DOI: 10.1016/j.biochi.2026.01.003

Kalina Wegrzyn, Tomasz Wilanowski

Phase separation underlies the formation of subcellular structures known as biomolecular condensates or membraneless organelles. In the last 15 years, a great effort has been made to characterize the biophysical properties of condensates and their role in cellular processes, including the regulation of gene expression. In this article, we provide an overview of mechanisms of phase separation in the cellular milieu, including the role of intrinsically disordered proteins, and present a repertoire of methods used to study condensate properties. Additionally, we describe recent advances regarding the role of phase separation in regulation of gene expression.

相分离是亚细胞结构形成的基础，称为生物分子凝聚物或无膜细胞器。在过去的15年里，人们已经做出了巨大的努力来表征凝析物的生物物理特性及其在细胞过程中的作用，包括基因表达的调节。在本文中，我们概述了细胞环境中相分离的机制，包括内在无序蛋白的作用，并介绍了用于研究凝析物性质的一系列方法。此外，我们描述了关于相分离在基因表达调控中的作用的最新进展。

引用次数: 0

Dietary modulation of purine metabolism and uric acid homeostasis in cancer patients with an ileostomy 回肠造口术后癌症患者嘌呤代谢和尿酸稳态的饮食调节。

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2026-01-05 DOI: 10.1016/j.biochi.2026.01.002

Kamil Aleksander Sobieszek , Jakub Frankowski , Mateusz Labudda

Nutritional management in cancer patients with an ileostomy poses specific challenges due to impaired nutrient absorption, elevated metabolic demands, and the need to control serum urate levels. This review examines the biochemical and clinical relevance of plant-based foods in addressing these issues, with particular emphasis on purine content, digestibility, and metabolic outcomes. Current evidence shows that legumes, soy products, nuts, seeds, whole grains, vegetables, fruits, and fortified foods generally contain low to moderate purine levels and are well tolerated by ileostomy patients. Incorporating these foods into individualized dietary plans supports adequate protein and micronutrient intake, enhances tissue repair, and reduces the risk of gout flares without compromising gastrointestinal function. Moreover, plant-derived bioactive compounds and antioxidants may mitigate inflammation and oxidative stress associated with cancer progression and hyperuricemia. Collectively, a carefully designed plant-based diet can meet the nutritional needs of cancer patients with an ileostomy while contributing to effective gout management and improved metabolic homeostasis.

由于营养吸收受损、代谢需求升高以及控制血清尿酸水平的需要，回肠造口术后癌症患者的营养管理面临着特殊的挑战。这篇综述探讨了植物性食物在解决这些问题方面的生化和临床相关性，特别强调嘌呤含量、消化率和代谢结果。目前的证据表明，豆类、豆制品、坚果、种子、全谷物、蔬菜、水果和强化食品通常含有低至中等水平的嘌呤，并且对回肠造口患者耐受良好。将这些食物纳入个性化的饮食计划有助于摄入足够的蛋白质和微量营养素，增强组织修复，并在不损害胃肠道功能的情况下降低痛风发作的风险。此外，植物源性生物活性化合物和抗氧化剂可能减轻与癌症进展和高尿酸血症相关的炎症和氧化应激。总的来说，精心设计的植物性饮食可以满足回肠造口癌患者的营养需求，同时有助于有效的痛风管理和改善代谢稳态。

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Reviewers acknowledgement 2025 审稿人确认2025

IF 3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimie

Pub Date : 2026-01-01 DOI: 10.1016/j.biochi.2025.12.007

引用次数: 0

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